Trial reportPharmacogenetics and genomics2014
Genomewide association study of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202.
Trial report in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing.Clinical pharmacology and therapeutics · 2016Guideline
- Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.Pharmacogenetics and genomics · 2015Pooled it
- Pharmacogenetic Analysis of the Model-Based Pharmacokinetics of Five Anti-HIV Drugs: How Does This Influence the Effect of Aging?Clinical and translational science · 2018Trial
- Multiphenotype association study of patients randomized to initiate antiretroviral regimens in AIDS Clinical Trials Group protocol A5202.Pharmacogenetics and genomics · 2017Trial
- Genomewide association study of tenofovir pharmacokinetics and creatinine clearance in AIDS Clinical Trials Group protocol A5202.Pharmacogenetics and genomics · 2015Trial
- Interactions between long-acting antiretrovirals and opioids: a call for clinical awareness.Clinical microbiology reviews · 2026Review
- Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Dose of ritonavir-boosted atazanavir for HIV patient: a reappraisal based on genetic polymorphism epidemiology in Southeast Asia.International journal of physiology, pathophysiology and pharmacology · 2022Article
- Review
- Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives.Pharmacogenetics and genomics · 2020Article
- Mitochondrial DNA Haplogroups and Frailty in Adults Living with HIV.AIDS research and human retroviruses · 2020Observational
- Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease.Pharmacogenomics and personalized medicine · 2020Review
- The dawn of precision medicine in HIV: state of the art of pharmacotherapy.Expert opinion on pharmacotherapy · 2018Review
- PharmGKB summary: atazanavir pathway, pharmacokinetics/pharmacodynamics.Pharmacogenetics and genomics · 2018Article
- Drug-Induced Kidney Stones and Crystalline Nephropathy: Pathophysiology, Prevention and Treatment.Drugs · 2018Review
- Race/ethnicity difference in the pharmacogenetics of bilirubin-related atazanavir discontinuation.Pharmacogenetics and genomics · 2018Observational
- Genetic Polymorphisms Affecting the Pharmacokinetics of Antiretroviral Drugs.Clinical pharmacokinetics · 2017Review
- Hyperbilirubinemia in atazanavir treated HIV-infected patients: the impact of the UGT1A1*28 allele.Pharmacogenomics and personalized medicine · 2017Review
- Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals.AIDS research and treatment · 2016Review
- Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection.HIV/AIDS (Auckland, N.Z.) · 2016Review
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundAtazanavir-associated hyperbilirubinemia can cause premature discontinuation of atazanavir and avoidance of its initial prescription. We used genomewide genotyping and clinical data to characterize determinants of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202.
methodsPlasma atazanavir pharmacokinetics and indirect bilirubin concentrations were characterized in HIV-1-infected patients randomized to atazanavir/ritonavir-containing regimens. A subset had genomewide genotype data available.
resultsGenomewide assay data were available from 542 participants, of whom 475 also had data on estimated atazanavir clearance and relevant covariates available. Peak bilirubin concentration and relevant covariates were available for 443 participants. By multivariate analysis, higher peak on-treatment bilirubin levels were found to be associated with the UGT1A1 rs887829 T allele (P=6.4×10(-12)), higher baseline hemoglobin levels (P=4.9×10(-13)), higher baseline bilirubin levels (P=6.7×10(-12)), and slower plasma atazanavir clearance (P=8.6×10(-11)). For peak bilirubin levels greater than 3.0 mg/dl, the positive predictive value of a baseline bilirubin level of 0.5 mg/dl or higher with hemoglobin concentrations of 14 g/dl or higher was 0.51, which increased to 0.85 with rs887829 TT homozygosity. For peak bilirubin levels of 3.0 mg/dl or lower, the positive predictive value of a baseline bilirubin level less than 0.5 mg/dl with a hemoglobin concentration less than 14 g/dl was 0.91, which increased to 0.96 with rs887829 CC homozygosity. No polymorphism predicted atazanavir pharmacokinetics at genomewide significance.
conclusionAtazanavir-associated hyperbilirubinemia is best predicted by considering UGT1A1 genotype, baseline bilirubin level, and baseline hemoglobin level in combination. Use of ritonavir as a pharmacokinetic enhancer may have abrogated genetic associations with atazanavir pharmacokinetics.
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Registered trials
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